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Stangl, S. ; Gehrmann, M. ; Dressel, R. ; Alves, F. ; Dullin, C. ; Themelis, G. ; Ntziachristos, V. ; Staeblein, E. ; Walch, A.K. ; Winkelmann, I. ; Multhoff, G.

In vivo imaging of CT26 mouse tumours by using cmHsp70.1 monoclonal antibody.

J. Cell. Mol. Med. 15, 874-887 (2011)
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The major stress-inducible heat shock protein 70 (Hsp70) is frequently present on the cell surface of human tumors, but not on normal cells. Herein, the binding characteristics of the cmHsp70.1 mouse monoclonal antibody (mAb) were evaluated in vitro and in a syngeneic tumor mouse model. More than 50% of the CT26 mouse colon carcinoma cells express Hsp70 on their cell surface at 4 degrees C. After a temperature shift to 37 degrees C, the cmHsp70.1-FITC mAb translocates into early endosomes and lysosomes Intraoperative and near-infrared fluorescence (NIRF) imaging revealed an enrichment of Cy5.5-conjugated mAb cmHsp70.1, but not an identically labelled IgG1 isotype-matched control, in i.p. and s.c. located CT26 tumors, as soon as 30min after i.v. injection into the tail vein. Due to the rapid turnover rate of membrane-bound Hsp70, the fluorescence-labelled cmHsp70.1 mAb became endocytosed and accumulated in the tumor, reaching a maximum after 24h and remained detectable at least up to 96h after a single i.v. injection. The tumor-selective internalization of mAb cmHsp70.1 at the physiological temperature of 37 degrees C might enable a targeted uptake of toxins or radionuclides into Hsp70 membrane-positive tumors. The anti-tumoral activity of the cmHsp70.1 mAb is further supported by its capacity to mediate antibody dependent cytotoxicity (ADCC).
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords membrane-bound Hsp70; Hsp70 antibody; tumor mouse model; flat panel volume CT; near-infrared fluorescence imaging
ISSN (print) / ISBN 1582-1838
e-ISSN 1582-4934
Journal Journal of Cellular and Molecular Medicine
Quellenangaben Volume: 15, Issue: 4, Pages: 874-887 Article Number: , Supplement: ,
Publisher Blackwell
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Innate Immunity in Tumor Biology (PATH-KTB)
Institute of Biological and Medical Imaging (IBMI)
Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)